The goal of the proposed research is to further develop and optimize our new screening strategy as a generally applicable method for the high throughput identification and ranking of lead compounds in the drug discovery process. This strategy was demonstrated in the Phase l period of this project to have several advantages that offer an approximately 8-fold greater throughput, and, in addition, a more widespread cross target utility than the conventional combinatorial library screening methodologies. We propose first to design and construct a new streamlined and customized instrument that will combine and coordinate the temperature cycling component of the microplate assay with the signal detection component into an integrated and automated high throughput lead discovery apparatus. A second key goal is to apply this tool to as many diverse therapeutic targets as possible.